We measured neural activity during negative emotional face versus shape matching in unmedicated depressed and healthy mothers to explore mechanisms of postpartum depression. There was a main effect of task condition such that faces were associated with increased amygdala activity and shapes were associated with increased dorsomedial prefrontal cortex activity in all women.
Our first novel finding was that negative emotional faces activated the left dorsomedial prefrontal cortex over a large region in Brodmann’s area 32 significantly less in depressed mothers than in healthy mothers. While activity in this region did not correlate with depressive severity or maternal attachment, relationships between symptom severity and activity in this region may have been masked by a potential floor effect of postpartum depression on face-related dorsomedial prefrontal cortex activity. The dorsomedial prefrontal cortex is involved in voluntary and automatic control and reappraisal of emotional responses (37
) and also in the social cognition network that allows an individual to recognize and consider the emotional experiences, values, and goals of others. Deficits in dorsomedial prefrontal cortex activity in response to negative faces in depressed mothers, therefore, might represent diminished awareness of and empathic responses to emotions of others, as has been reported in individuals with postpartum and nonpostpartum depression (37
Our second novel finding was that preceding (top-down) connectivity between the left dorsomedial prefrontal cortex and left amygdala during negative emotional faces was present only in healthy, and not depressed, mothers. The presence of strong dorsomedial prefrontal cortex-amygdala effective connectivity in healthy mothers might represent a neural circuitry that supports social, empathic processes for regulation of amygdala activity in response to negative emotional stimuli. Engagement of this circuitry would be highly adaptive for generating optimal responses to environmental or infant challenges for new mothers. The absence of dorsomedial prefrontal cortex-amygdala connectivity during processing of negative emotional faces in depressed mothers, combined with reduced activity in the dorsomedial prefrontal cortex in response to these faces, suggests a disengagement of a critical prefrontal cortico-limbic circuitry for effective automatic emotional appraisal and voluntary regulation of emotional arousal in postpartum depression (38
Our findings refuted our hypothesis, and contrasted with preliminary reports (20
), that depressed mothers would show abnormal activity in the amygdala in response to negative emotional stimuli. While some studies reported greater (22
) and more sustained (39
) amygdala activity in response to negative emotional stimuli in nonpostpartum depressed adults relative to healthy adults, this finding has not been universal (40
). The absence of amygdala hyperactivity in response to faces in depressed mothers relative to healthy mothers could also be explained by diminished hypothalamic-pituitary-adrenal axis drive following childbirth in women with postpartum “blues” and depression (7
). Alternatively, the absence of elevated left amygdala activity in response to these cues in depressed mothers, which may have been predicted to result from the diminished top-down regulation of the left amygdala by the left dorsomedial prefrontal cortex, might have resulted from our finding that greater postpartum depression severity was in fact associated with reduced, not greater, left amygdala activity in response to negative emotional faces in depressed mothers. The impact of diminished top-down regulation of the left amygdala by the left dorsomedial prefrontal cortex may therefore have been lessened by this second finding of a negative relationship between postpartum depression severity and left amygdala activity in response to negative emotional faces in the more depressed mothers. It is also possible that our sample may have been too small to detect a significant between-group difference in amygdala activity, although we were able to detect a group-by-condition interaction in the dorsomedial prefrontal cortex.
Previous theories link approach and withdrawal-related emotion processing with left and right hemispheres, respectively (42
). In our findings, left lateralization remained significant even after a reduction of the voxel-wise error rate to a liberal p value <0.05. It is therefore possible that our predominantly left-sided findings regarding dorsomedial prefrontal cortical activity, dorsomedial prefrontal cortical-amygdala connectivity, and relationships between symptom severity and amygdala activity in depressed mothers may reflect dysfunctional processing particular of approach-related emotional cues. While our study was not powered to formally test the laterality effect in our regions of interest, further studies could examine this effect.
This is the first study, to our knowledge, to examine negative face processing in postpartum depressed and healthy mothers. While a limitation was the relatively modest sample of participants, one strength of the study was the inclusion of unmedicated, largely antidepressant-naive, depressed mothers. Additionally, participant groups were well-matched for demographic, medical, and obstetric factors as well as behavioral performance. Future study of a larger sample will allow examination of the contributing roles of psychiatric comorbidity in postpartum depressed mothers, breast-feeding status, timing of depression onset, and parity to create an integrative model of risk for the neural circuitry deficits of interest.
Our finding that greater infant-related hostility was associated with reduced face-related right amygdala activity suggests that this might be a neural substrate for the reduced attunement and empathic responses reported among depressed mothers. It will be important to build upon our present findings with concurrent behavioral assessments of the mother-infant relationship to clarify neural mechanisms of mother-infant attachment.
In conclusion, diminished dorsomedial prefrontal cortical activity, diminished dorsomedial prefrontal cortical-amygdala effective connectivity, and a negative relationship of depression severity to amygdala activity may be important mechanisms or effects of postpartum depression. These preliminary findings, if replicated, may be useful biological targets that can be used to guide the development of more effective treatments for postpartum depression.